Friday, October 01, 2010

FDA Guidelines for Determining Eligibility for Advisory Committees are Ridiculous and Ensure that Conflicts of Interest Will Continue to Plague Agency

Yesterday, I called for the removal of four FDA Tobacco Products Scientific Advisory Committee (TPSAC) panel members - Dr. Neal Benowitz, Dr. Jack Henningfield, Dr. Dorothy Hatsukami, and Dr. Jonathan Samet - because they have significant conflicts of interest with pharmaceutical companies that make it impossible for them to offer objective advice to the Agency on federal tobacco regulatory policy.

A major issue that the panel will soon consider is regulation of dissolvable tobacco products. These are a direct threat to the profits of pharmaceutical companies because they may be used as an alternative for smoking cessation. The threat is so significant that GlaxoSmithKline petitioned the FDA to remove these products from the market.

As I revealed, the rest of the story is that Dr. Henningfield is a GlaxoSmithKline consultant. Clearly, it is unacceptable for Dr. Henningfield to remain on the panel. Similarly, Dr. Benowitz and Dr. Samet should be removed from the panel because they have either consulted for or received grant support from GlaxoSmithKline. Dr. Hatsukami did not receive Glaxo support but did receive funding from another pharmaceutical company to research a nicotine vaccine.

Today, I reveal that the procedure used by the FDA to determine eligibility for participation on advisory panels is severely flawed and essentially guarantees that the Agency will continue to be plagued by conflicts of interest.

Research has shown that FDA advisory committee panelists' conflicts of interest affect their voting behavior. Based on this research, Public Citizen had threatened to sue the FDA to force elimination or remediation of these conflicts (a threat which should be renewed based on the analysis I am about to report).

The Rest of the Story

While the FDA made it look like it was addressing these concerns by adopting new guidelines regarding conflicts of interest in August 2008, an examination of these guidelines reveals that they are woefully inadequate and inappropriate and demonstrate a profound misunderstanding of the problem of conflicts of interest.

A conflict of interest policy should be designed to ensure that decisions regarding federal policy are not influenced by financial conflicts of interest of panel members. The way to do this is to determine what constitutes a disqualifying conflict of interest and then not to allow any scientist with such a conflict to serve on an advisory panel.

Instead of adopting such an approach, the FDA completely copped out by making it look like the Agency was going to disqualify scientists with conflicts of interest, but then giving the Agency the opportunity to nevertheless allow such scientists to serve on the panels.

The FDA guidelines accomplish this in three ways:

1. Waivers

First, the FDA has allotted itself a certain number of waivers. These waivers are essentially free passes, where a conflicted scientist can still be appointed to a panel as long as the the FDA hasn't used up its waiver quota.

While federal law allows the FDA to grant these waivers, the FDA is under no requirement to do so. The FDA has admitted it has created a problem by granting these waivers, but instead of agreeing to eliminate the waivers the FDA has simply agreed to reduce the number of the waivers.

What the FDA apparently fails to understand is that there is no waiver of an otherwise disqualifying conflict of interest. Either an individual has a disqualifying conflict of interest or she does not. If you start making waivers, you are essentially gutting the conflict of interest policy and destroying its entire purpose. You are ensuring that conflicts of interest will continue to plague the Agency's decision-making.

2. Exceptions for Scientific Expertise

The conflict of interest policy goes out the window if the FDA declares that a scientist's potential contribution to an advisory panel outweighs the potential for a conflict of interest. This is obviously an arbitrary or subjective judgment which allows the Agency complete reign to continue allowing conflicted scientists to serve on these advisory panels.

Such a policy is completely ignorant of the purpose of conflict of interest guidelines: to eliminate the formulation of federal policy by conflicted scientists. Every scientist that will be considered for a panel has special scientific expertise and one could always make an argument that his expertise outweighs the potential for a conflict of interest. You see, conflicts of interest are only severe when they actually occur. Looking in advance at a situation, one will never see the tremendous damage that could be done. It is a flawed premise from the start that one can make a judgment, in advance, about how a conflict is going to play out in the future.

Either a conflict of interest is disqualifying or it is not. Either the FDA is committed to ensuring that federal regulatory policy decisions are made by unconflicted scientists or it is not. Putting waivers and subjective judgments of scientific expertise into the procedure has the effect of completely gutting the policy and destroying the very purpose for which the policy exists in the first place.

3. High Threshold for Level of Disqualifying Conflicts of Interest

While some universities set a threshold of $10,000 per year for the amount below which a conflict of interest is not disqualifying, the FDA has set that level at a whopping $50,000. Even a lower threshold has little validity, because there is no evidence that conflicts of interest no longer bias decision-making when the conflict is below a certain amount. But it should be clear to all readers that a conflict at the level of tens of thousands of dollars, even if it does not exceed $50,000 a year, is a huge financial interest.

Let's face it - $49,999 per year is more than most U.S. households make. To be exact, 53% of U.S. households bring in less than $50,000 in income in total. To declare that only above $50,000 a year does a financial interest become disqualifying is insane. It's also insulting, frankly. Are we really to believe that someone who makes $40,000 per year from GlaxoSmithKline consulting is going to nevertheless be completely objective in making a decision that could devastate the company's profits? There is no rational basis for this income threshold and once again, it undermines the entire purpose of the conflict of interest policy.

The End Result? No Effective Conflict of Interest Protection

As we are observing with the Tobacco Products Scientific Advisory Committee - which is a virtual boardroom full of pharmaceutical company (smoking cessation drug) consultants, the FDA's conflict of interest policy is not working. It is essentially no policy at all.

The ineffectiveness of the policy is perhaps best seen by the recent revelation that one of the FDA advisory panel members who voted to keep Avandia on the market without any additional warnings or restrictions was a paid speaker for GlaxoSmithKline, the manufacturer of Avandia. On the same panel, another scientist - this one who voted to remove Avandia from the market - had been a paid speaker for a rival pharmaceutical company which manufactures a competing drug.

It should be noted that these conflicts were on the order of just a few thousands of dollars per year, making the $50,000 limit for disqualifying conflicts of interest a complete joke.

Frankly, the entire policy is a complete joke. It does nothing to prevent the formulation of federal regulatory policy by scientists who have significant financial conflicts of interest.

Seeing how the FDA is not going to remove the conflicted TPSAC panelists, I hope Dr. Benowitz, Dr. Samet, Dr. Hatsukami, and Dr. Henningfield will voluntarily withdraw from the advisory panel due to their clearly disqualifying conflicts of interest. The FDA may be willing to grant them waivers, but these scientists should play no part in promoting the continuing plague of industry influence on federal public health decision-making.

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About Me

Dr. Siegel is a Professor in the Department of Community Health Sciences, Boston University School of Public Health. He has 25 years of experience in the field of tobacco control. He previously spent two years working at the Office on Smoking and Health at CDC, where he conducted research on secondhand smoke and cigarette advertising. He has published nearly 70 papers related to tobacco. He testified in the landmark Engle lawsuit against the tobacco companies, which resulted in an unprecedented $145 billion verdict against the industry. He teaches social and behavioral sciences, mass communication and public health, and public health advocacy in the Masters of Public Health program.